The impact of delayed diagnosis and treatment due to COVID-19 on Australian thyroid cancer patients: a qualitative interview study.

OBJECTIVES: The study aims to investigate the perceptions of patients with thyroid cancer on the potential impact of diagnosis and treatment delays during the COVID-19 pandemic. DESIGN: This study involved qualitative semi-structured telephone interviews. The interviews were transcribed verbatim, analysed using the thematic framework analysis method and reported using the Consolidated Criteria for Reporting Qualitative Research. SETTING: Participants in the study were treated and/or managed at hospital sites across New South Wales and Victoria, Australia. PARTICIPANTS: 17 patients with thyroid cancer were interviewed and included in the analysis (14 females and 3 males). RESULTS: The delays experienced by patients ranged from <3 months to >12 months. The patients reported about delays to diagnostic tests, delays to surgery and radioactive iodine treatment, perceived disease progression and, for some, the financial burden of choosing to go through private treatment to minimise the delay. Most patients also reported not wanting to experience delays any longer than they did, due to unease and anxiety. CONCLUSIONS: This study highlights an increased psychological burden in patients with thyroid cancer who experienced delayed diagnosis and/or treatment during COVID-19. The impacts experienced by patients during this time may be similar in the case of other unexpected delays and highlight the need for regular clinical review during delays to diagnosis or treatment.

Surgical Management of Indeterminate Thyroid Nodules across Different World Regions: Results from a Retrospective Multicentric (the MAIN-NODE) Study.

Indeterminate thyroid nodules (ITNs) are characterized by an expected malignancy ranging from 5% to 30%, with most patients undergoing a diagnostic, rather than therapeutic, operation. The aim of our study was to compare the approach to ITNs across different regions of the world. In this retrospective, multicentric, international study, according to the WHO classification, we identified the South East Asian Region (SEAR), the Americas Region (AMR), the Eastern Mediterranean Region (EMR), the Europe Region (EUR), and the Western Pacific Region (WPR). One high-volume thyroid centre was included for each region. Demographic, preoperative, and pathologic data were compared among the different regions. Overall, 5737 patients from five high-volume thyroid centres were included in this study. We found that the proportion of ITNs over the global activity for thyroid disease was higher in the EUR (37.6%) than in the other regions (21.1-23.6%). In the EMR, the patients were significantly younger (with a mean of 43.1 years) than in the other regions (range, 48.8-57.4 years). The proportion of lobectomy was significantly higher in the WPR, where 83.2% (114/137) of patients received this treatment, than in the other regions, where lobectomies were performed in 44.1-58.1% of patients. The pathological diagnosis of malignancy was significantly higher in the SEAR centre, being over 60%, than in centres of the other regions, where it ranged from 26.3% to 41.3%. The occurrence of lymph node metastases was higher in the WPR (27.8%), AMR (26.9%), and EMR (20%) centres than in the EUR and SEAR centres, where it was lower than 10%. In summary, we found in our study different approaches and outcomes in the diagnosis and treatment of ITNs among countries. Overall, almost 60% of patients with ITNs who underwent surgery actually presented a benign disease, potentially undergoing an unnecessary operation.

The role of seabird guano in maintaining North Atlantic summertime productivity.

Nutrients supplied via seabird guano increase primary production in some coastal ecosystems. A similar process may occur in the open ocean. To investigate this directly, we first measured bulk and leachable nutrient concentrations in guano sampled in the North Atlantic. We found that guano was strongly enriched in phosphorus, which was released as phosphate in solution. Nitrogen release was dominated by reduced forms (ammonium and urea) whilst release of nitrate was relatively low. A range of trace elements, including the micronutrient iron, were released. Using in-situ bioassays, we then showed that supply of fresh guano to ambient seawater increases phytoplankton biomass and photochemical efficiencies. Based on these results, modelled seabird distributions, and known defecation rates, we estimate that on annual scales guano is a minor source of nutrients for the surface North Atlantic. However, on shorter timescales in late spring/summer it could be much more important: Estimates of upper-level depositions of phosphorus by seabirds were three orders of magnitude higher than modelled aerosol deposition and comparable to diffusion from deeper waters.

2021 Asia-Pacific Graves' Disease Consortium Survey of Clinical Practice Patterns in the Management of Graves' Disease.

AIM: Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe. METHODS: A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions. RESULTS: A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and ß-blockers and adjunctive ATD-treatment during RAI in the APAC-group. CONCLUSION: Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts.

Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment.

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.

Primary hyperparathyroidism in adults-(Part I) assessment and medical management: Position statement of the endocrine society of Australia, the Australian & New Zealand endocrine surgeons, and the Australian & New Zealand bone and mineral society.

OBJECTIVE: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions. RESULTS: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. CONCLUSIONS: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community.

Primary hyperparathyroidism in adults-(Part II) surgical management and postoperative follow-up: Position statement of the Endocrine Society of Australia, The Australian & New Zealand Endocrine Surgeons, and The Australian & New Zealand Bone and Mineral Society.

OBJECTIVE: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions. RESULTS: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended. CONCLUSIONS: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism.

Evolution of surgical management for phaeochromocytoma over a 17-year period: an Australian perspective.

BACKGROUND: Minimally invasive adrenalectomy and advances in anaesthetic techniques have transformed surgery for phaeochromocytoma. This 17-year review describes the evolution of phaeochromocytoma care in our unit. METHODS: We performed a retrospective cohort review of all patients who underwent adrenalectomy for phaeochromocytoma from 2000 to 2016. Patients were divided into three time periods, early: 2000-2005 (n = 17), middle: 2006-2010 (n = 15) and late: 2011-2016 (n = 24). The posterior retroperitoneoscopic adrenalectomy was introduced in 2011. Demographics and clinicopathological details were extracted. Median values for nominal data were compared using Mann-Whitney U-test. A chi-squared test was used to compare categorical data. RESULTS: Sixty-one adrenalectomies were performed on 56 patients: 19 open, 17 laparoscopic and 20 posterior retroperitoneoscopic adrenalectomies. The median length of operation decreased from 135 to 90 min from the early to the late time period (P > 0.05). Length of stay decreased from a median of 5 days in the early group to 1 day in the late group (P = 0.01). A total of 94.1% of the early period patients were admitted to the intensive care unit compared to 30.4% of the late group (P = <0.01). Need for post-operative vasopressors and blood transfusions was significantly reduced. CONCLUSION: Over the 17-year period, the choice of operative technique has transitioned towards posterior retroperitoneoscopic adrenalectomy. Operative time, rate of intensive care unit admission, and admission length have all decreased without any increase in rates of complications.

The impact of public performance reporting on cancer elective surgery waiting times: a data linkage study.

BACKGROUND: Excessive waiting times for cancer elective surgery are a concern in publicly funded healthcare systems. Several countries including Australia have introduced healthcare reforms involving time-based targets and public performance reporting (PPR) of hospital data. However, there is mixed evidence of their benefits. We sought to examine the impact of targets and PPR of cancer elective surgery waiting times on access to breast, bowel and lung cancer elective surgery. METHODS: We analysed routinely-collected linked data on admissions and waiting times for patients aged 15 years or over (n = 199,885) who underwent cancer surgery in a public hospital in Victoria, Australia over a 10-year period. We conducted difference-in-differences analyses to compare waiting times before (2006-07 to 2011-12) and after (2012-13 to 2015-16) the introduction of PPR in meeting these targets. RESULTS: Across all cancer types, urgent patients were all treated within 30 days before and after PPR. Following PPR, there was a slight increase in the mean waiting times across all cancer types and urgency categories. Patients with lung cancer waited on average two and half days longer for treatment and patients with breast cancer waited on average half-a-day less. There was no effect of PPR on waiting times for patients with bowel cancer across urgency categories. CONCLUSIONS: Our findings suggest that time-based targets and PPR had minimal impact on surgical waiting times. This may be due to reasonable waiting times prior to PPR, improved efficiency being masked by 20% growth in the population, lack of public knowledge that waiting times are publicly reported, or lack of real-time reporting to drive behavioural change. The use of generic elective surgery recommended waiting time measures for cancer is discussed.

Bi-national Review of Phaeochromocytoma Care: Is ICU Admission Always Necessary?

BACKGROUND: Post-operative management after phaeochromocytoma resection includes monitoring of blood pressure and blood sugar, and vigilance for haemorrhage. Guidelines recommend 24 h of continuous blood pressure monitoring, usually necessitating HDU/ICU admission. We hypothesised that most patients undergoing phaeochromocytoma resection do not require post-operative HDU/ICU admission. We aim to describe current Australian and New Zealand perioperative management of phaeochromocytoma and determine whether it is safe to omit HDU/ICU care for most patients. METHODS: We collected retrospective data on patients undergoing excision of phaeochromocytoma in 12 centres around Australia and New Zealand between 2007 and 2019. Data collected included preoperative medical management, anaesthetic management, vasopressor support, HDU/ICU admission and complications. RESULTS: A total of 223 patients were included in the study, 173 (77%) of whom were admitted to HDU/ICU post-operatively. The group of patients treated in ICU was similar to the group of patients treated on the ward in terms of demographic and tumour characteristics, and there were significant differences in the proportion of patients admitted to HDU/ICU between centres. Of patients admitted to ICU, 71 (41%) received vasopressor support. This was weaned within 24 h in 55 (77%) patients. Patients with larger tumours (> 6 cm) and a transfusion requirement are more likely to require prolonged inotropic support. Among patients admitted to the ward, there were no complications that required escalation of care. CONCLUSIONS: Although not widespread practice in Australia and New Zealand, it appears safe for the majority of patients undergoing minimally invasive resection of phaeochromocytoma to be admitted to the ward post-operatively.

Radioactive iodine ablation post differentiated thyroid cancer surgery: an analysis of use and impact of the American Thyroid Association guidelines.

BACKGROUND: The 2009 American Thyroid Association (ATA) three-tiered risk stratification, and its updated version in 2015, provided clearer guidance on the use of radioactive iodine (RAI) ablation in differentiated thyroid cancer (DTC) patients. This study examines the impact of these guidelines on RAI use in our institution. METHODS: Patients diagnosed with DTC during three different time periods (group 1: 2002-2006, group 2: 2010-2014 and group 3: 2017-2018) were identified and risk stratified according to the ATA guidelines. RAI use and extent of surgery were compared between the three groups. Categorical variables were analysed using Fisher's exact (2 × 2) and chi-squared (>2 × 2) tests. RESULTS: A total of 415 patients were included (group 1 = 88, group 2 = 215, group 3 = 112). The proportion of patients having total thyroidectomy were 84.6, 84.7 and 69.6% in groups 1, 2 and 3, respectively (P = 0.003). Central lymph node dissection was significantly higher in the more contemporary groups compared to group 1 (9.1 versus 41.9 versus 64.3%, P < 0.001). Overall, fewer patients received RAI in more recent times (76.6 versus 54.8 versus 26.8%, P < 0.001), most evident in the low-risk patients (70 versus 29.1 versus 5.1%, P < 0.001). In the high risk group, the majority received RAI, with no difference between the groups. CONCLUSION: Comparing DTC patients treated in our unit before and after publications of the 2009 and 2015 ATA guidelines, more nodal surgery was performed with less RAI administered in the latter groups. Better risk stratification according to the ATA guidelines has allowed more judicious use of RAI ablation.

Practice Patterns in Parathyroid Surgery: A Survey of Asia-Pacific Parathyroid Surgeons.

BACKGROUND: Practice variations exist amongst parathyroid surgeons depending on their expertise and resources. Our study aims to elucidate the choice of surgical techniques and adjuncts used in parathyroid surgery by surgeons in the Asia-Pacific region. METHODS: A 25-question online survey was sent to members of five endocrine surgery associations. Questions covered training background, practice environment and preferred techniques in parathyroid surgery. Respondents were divided into three regions: Australia/New Zealand, South/South East Asia and East Asia, and responses were analysed according to region, specialty, case volume and years in practice. RESULTS: One hundred ninety-six surgeons returned the questionnaire. Most surgeons (98%) routinely perform preoperative imaging, with 75% preferring dual imaging with 99mTcsestamibi and ultrasound. Ten per cent of surgeons use parathyroid 4DCT as first-line imaging, more commonly in East Asia (p = 0.038). Minimally invasive parathyroidectomy is the favoured technique of choice (97%). Most surgeons reporting robotic or endoscopic approaches are from East Asia. Rapid intraoperative parathyroid hormone is accessible to just under half of the surgeons but less available in Australian/New Zealand (p < 0.001). The use of intraoperative neuromonitoring is not commonly used, even less so amongst Asian surgeons (p = 0.048) and surgeons with low case load (p = 0.013). CONCLUSION: Dual localisation techniques are the preferred choice of investigations in preparation for parathyroid surgery, with minimally invasive surgery without neuromonitoring the preferred approach. Use of adjuncts is sporadic and limited to certain centres.

Development of a binational thyroid cancer clinical quality registry: a protocol paper.

INTRODUCTION: The occurrence of thyroid cancer is increasing throughout the developed world and since the 1990s has become the fastest increasing malignancy. In 2014, a total of 2693 Australians and 302 New Zealanders were diagnosed with thyroid cancer, with this number projected to rise to 3650 in 2018. The purpose of this protocol is to establish a binational population-based clinical quality registry with the aim of monitoring and improving the quality of care provided to patients diagnosed with thyroid cancer in Australia and New Zealand. METHODS AND ANALYSIS: The Australian and New Zealand Thyroid Cancer Registry (ANZTCR) aims to capture clinical data for all patients over the age of 16 years with thyroid cancer, confirmed by histopathology report, who have been diagnosed, assessed or treated at a contributing hospital. A multidisciplinary steering committee was formed which, with operational support from Monash University, established the ANZTCR in early 2017. The pilot phase of the registry is currently operating in Victoria, New South Wales, Queensland, Western Australia and South Australia, with over 20 sites expected to come on board across Australia in 2018. A modified Delphi process was undertaken to determine the clinical quality indicators to be reported by the registry, and a minimum data set was developed comprising information regarding thyroid cancer diagnosis, pathology, surgery and 90-day follow-up. FUTURE PLANS: The establishment of the ANZTCR provides the opportunity for Australia and New Zealand to further understand current practice in the treatment of thyroid cancer and identify variation in outcomes. The engagement of endocrine surgeons in supporting this initiative is crucial. While the pilot registry has a focus on early clinical outcomes, it is anticipated that future collection of longer term outcome data particularly for patients with poor prognostic disease will add significant further value to the registry.